Language
English
Publication Date
8-13-2025
Journal
mBio
DOI
10.1128/mbio.01180-25
PMID
40631898
PMCID
PMC12345152
PubMedCentral® Posted Date
7-9-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Human norovirus (HuNoV) causes acute gastroenteritis in immunocompetent hosts and chronic infection in immunocompromised individuals. Many recent studies of replication and innate immune responses following HuNoV infection have utilized epithelium-only human intestinal enteroids (HIEs), which lack immune cells. Here, we utilized an ex vivo enteroid-macrophage coculture model consisting of HIEs and different subtypes of human peripheral blood mononuclear cell-derived macrophages to better recapitulate in vivo gut biology and explore the role of macrophages in HuNoV replication and pathogenesis. We show that HuNoV infection in HIEs polarized on Transwells leads to bilateral release of the viral genome, with predominant apical virus release. Coculture with naïve M0, pro-inflammatory M1, or anti-inflammatory M2 macrophages does not change levels of HuNoV replication. We found that macrophages respond to HuNoV infection by phagocytosis of virus-infected cells with pro-inflammatory M1 macrophages exhibiting the greatest phagocytic activity. Apical release of chemokines (IP-10, MIP-1α, and RANTES), acute-phase inflammatory mediators (IL-1α, IL1-RA, IL-6, and TNF-α), and anti-inflammatory mediators IL-10 and IL-1RA are increased following HuNoV infection only in HIEs cocultured with activated macrophages. These findings underscore the importance of epithelial-macrophage crosstalk in chemokine production during the early stages of infection required for leukocyte recruitment and initiation of the host response.
Keywords
Humans, Norovirus, Macrophages, Coculture Techniques, Phagocytosis, Caliciviridae Infections, Virus Replication, Cytokines, Organoids, human norovirus, intestinal enteroids, macrophages, phagocytosis, innate immunity
Published Open-Access
yes
Recommended Citation
Li, Ngan Fung; Crawford, Sue E; Mittiga, Sydney R; et al., "Macrophage Phagocytosis of Human Norovirus-Infected Cells in an Ex Vivo Human Enteroid-Macrophage Coculture Model" (2025). Faculty and Staff Publications. 4697.
https://digitalcommons.library.tmc.edu/baylor_docs/4697